CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain

Hidetoshi Mori, Taizo Tomari, Naohiko Koshikawa, Masahiro Kajita, Yoshifumi Itoh, Hiroshi Sato, Hideaki Tojo, Ikuo Yana, Motoharu Seiki

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Membrane-type 1 matrix metalloproteinase (MT1-MMP) localizes at the front of migrating cells and degrades the extracellular matrix barrier during cancer invasion. However, it is poorly understood how the polarized distribution of MT1-MMP at the migration front is regulated. Here, we demonstrate that MT1-MMP forms a complex with CD44H via the hemopexin-like (PEX) domain. A mutant MT1-MMP lacking the PEX domain failed to bind CD44H and did not localize at the lamellipodia. The cytoplasmic tail of CD44H, which comprises interfaces that associate with the actin cytoskeleton, was important for its localization at lamellipodia. Overexpression of a CD44H mutant lacking the cytoplasmic tail also prevented MT1-MMP from localizing at the lamellipodia. Modulation of F-actin with cytochalasin D revealed that both CD44H and MT1-MMP co-localize closely with the actin cytoskeleton, dependent on the cytoplasmic tail of CD44H. Thus, CD44H appears to act as a linker that connects MT1-MMP to the actin cytoskeleton and to play a role in directing MT1-MMP to the migration front. The PEX domain of MT1-MMP was indispensable in promoting cell migration and CD44H shedding.

Original languageEnglish (US)
Pages (from-to)3949-3959
Number of pages11
JournalEMBO Journal
Volume21
Issue number15
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

Fingerprint

Hemopexin
Matrix Metalloproteinase 14
Pseudopodia
Actins
Actin Cytoskeleton
Cytochalasin D
Cell Movement
Extracellular Matrix
Modulation

Keywords

  • Actin
  • CD44
  • Invasion
  • Lamellipodium
  • MT1-MMP

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. / Mori, Hidetoshi; Tomari, Taizo; Koshikawa, Naohiko; Kajita, Masahiro; Itoh, Yoshifumi; Sato, Hiroshi; Tojo, Hideaki; Yana, Ikuo; Seiki, Motoharu.

In: EMBO Journal, Vol. 21, No. 15, 01.08.2002, p. 3949-3959.

Research output: Contribution to journalArticle

Mori, H, Tomari, T, Koshikawa, N, Kajita, M, Itoh, Y, Sato, H, Tojo, H, Yana, I & Seiki, M 2002, 'CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain', EMBO Journal, vol. 21, no. 15, pp. 3949-3959. https://doi.org/10.1093/emboj/cdf411
Mori, Hidetoshi ; Tomari, Taizo ; Koshikawa, Naohiko ; Kajita, Masahiro ; Itoh, Yoshifumi ; Sato, Hiroshi ; Tojo, Hideaki ; Yana, Ikuo ; Seiki, Motoharu. / CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. In: EMBO Journal. 2002 ; Vol. 21, No. 15. pp. 3949-3959.
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